title: Biphasic response of mitochondrial biogenesis to oxidative stress in visceral fat of diet-induced obesity mice.
abstract: OBJECTIVE
  Studies in skeletal muscle demonstrate a strong association of mitochondrial dysfunction with insulin resistance (IR). However, there is still a paucity of knowledge regarding the alteration of mitochondria in adipose tissue (AT) in the pathogenesis of IR in obesity. We investigated the mitochondrial biogenesis in visceral fat (VF) and subcutaneous fat (SF) in C57BL/6J mice fed a high-fat high-sucrose diet for 12 months.
  
  
  RESULTS
  Impairment of glucose tolerance and insulin sensitivity developed after 1 month of the diet and was associated with a prompt increase of VF. The VF adipocytes were larger than those in the SF and had increased expressions of HIF-1α and p-NFκB p65. However, the alteration of mitochondrial biogenesis did not occur in the early stage when increased intracellular reactive oxygen species (ROS), mitochondrial oxygen consumption rate, and mitochondrial ROS emerged at the 1st, 2nd and 2nd month, respectively. Until the 6th month, the VF had markedly increased mitochondrial DNA content and expression of PGC-1α, Tfam, ATP5A, and MnSOD. This increase of mitochondrial biogenesis was followed by a generalized decrease at the 12th month and the mitochondrial morphology altered markedly. In the late stage, although mitochondrial ROS decreased, the increased expression of 8-OHdG in VF continued.
  
  
  CONCLUSIONS
  These data suggest that IR and ROS production occur before the biphasic changes of mitochondrial biogenesis in AT, and the VF plays a more crucial role.
authors.affiliation: 1 Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung Chang Gung Memorial Hospital , Kaohsiung, Taiwan .
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
authors.forename: Hsiao-Mei
authors.initials: HM
authors.lastname: Kuo
authors.forename: Hung-Tu
authors.initials: HT
authors.lastname: Huang
authors.forename: Alice Y W
authors.initials: AY
authors.lastname: Chang
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Weng
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
authors.forename: I-Ya
authors.initials: IY
authors.lastname: Chen
authors.forename: Shun-Chen
authors.initials: SC
authors.lastname: Huang
authors.forename: Tsu-Kung
authors.initials: TK
authors.lastname: Lin
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Liou
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005951:Glucose Tolerance Test; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species